Hybridoma technology will be employed to study the fine specificities and idiotypic relatedness of human lupus autoantibodies. We will prepare hybridomas by fusion of mutagenized human myeloma cells with B lymphocytes from the blood of patients with systemic lupus erythematosus. Hybridoma products will be screened for their ability to bind DNA, histones, and cardiolipin. We will characterize the fine specificities of the hybridoma autoantibodies by means of competitive immunoassays. We will also test the ability of monoclonal lupus autoantibodies to bind to neuronal cells and to lymphocytes. Anti-idiotypic antibodies will be prepared by immunization of rabbits with the hybridoma autoantibodies. We will then analyze idiotypic relatedness among a panel of hybridoma autoantibodies and measure, by immunoassay, serum levels of the idiotypes in lupus patients and their immediate relatives. Idiotypes on lymphocyte surfaces will be sought with fluorescein-tagged anti-idiotypic sera. Finally, fine specificities and idiotypic relatedness of autoantibodies from patients with drug-induced lupus will be studied and compared with those from patients with spontaneous lupus.